Inflammatory or allergic dermopathies may be a cause of physical and psychological problems for human beings and animals. For some of these diseases, such as psoriasis, there is no cure yet. Psoriasis is a chronic and recurrent disease. The cause of the accelerated cell growth of psoriasis is unknown, but immune mechanisms are thought to play an important role.
Peptide T is an octapeptide of sequence ASTTTNYT corresponding to a gp120 protein sequence segment of the human immunodeficiency virus. The analysis of its pharmacological profile shows that peptide T is effective in the treatment of psoriasis (cf. E. M. Faber et al., Proc. Natl. Acad. Sci. 1991, vol. 25, p. 658; T. Talme et al., Proc. Natl. Acad. Sci. 1995, vol. 287, p. 553). However, the use of peptide T as a medication is not advisable because of its low absorption, metabolic instability and immunogenic effects. As there is not yet a completely satisfactory treatment for psoriasis, it is of great interest to develop new antipsoriasis drugs.
From structure-activity studies based on the chemotactic properties of peptide T analogues (cf. M. Marastoni et al., Int. J. Pept. Proetin Res. 1993, vol. 41, pp. 441-454), a model of the bioactive conformation of peptide T was proposed (cf. N. B. Centeno et al., J. Comp.-Aided Mol. Design 1998, vol. 12, p. 7-14). In addition, this study has led to define a pharmacophore as well as its required positions for a good chemotactic activity of monocytes (cf. O. Llorens et al., Left. Pent. Sci. 1998, vol. 5, pp. 179-182). This pharmacophore was later used for in silico assays of different databases for compounds, which led to the natural product amygdalin (VII) as peptidomimetic of peptide T. Subsequent chemotaxis studies have demonstrated that amygdalin (VII) exhibits a chemotactic profile similar to that of peptide T and, consequently, a presumable similar antipsoriatic activity (cf. O. Llorens et al., Bioorg. Med. Chem. Left. 1998, vol. 8, pp. 781-786). Nevertheless, amygdalin (VII) is a natural product having a toxic profile. Its toxicity is known to be due to the release of cyanide ions in vivo.
